Alzheimer's disease (AD) platelets are the only cells in circulating blood to contain and secrete significant quantities of amyloid beta protein precursor (APP) found in abundance in senile plaques and neurofibrillary tangles, the lesions characteristically present in brains from AD patients. Our long term goal is to fully characterize the morphology, biochemistry and physiology of AD platelets and their relationship to the pathogenesis of the disease. Specifically, we will use ultrastructural immunocytochemistry to localize APP to alpha granules or other organelles in resting AD platelets and follow secretion of APP to the exterior following suspension activation or to subendothelium after surface activation. Micropipette elastimetry will determine if the increased fluidity of internal membranes is reflected in increased deformability of AD platelets. The nature of the internal membranes reported to accumulate in AD platelets will be determined by ultrastructural cytochemical procedures selective for the open canalicular system and dense tubular system. Effects of increased concentrations of APP and internal membrane accumulation on calcium flux, prostaglandin synthesis, and AD platelet function and structure during long-term storage will be studied in detail. We will also evaluate the influence of peptide homologues of APP on normal platelet structure, biochemistry and function. The proposed studies will provide the basic information essential to clarify the influence of increased APP and accumulated membranes on the pathophysiology of platelets in AD.